In the field of biocompatible polymers, polymers have been employed instead of various medical treatments and bodies. Recently, biodegradable polymers or amphiphilic polymers having both hydrophobicity and hydrophilicity have been of interest. Particularly, drug carriers changing molecular structure and controlling sol-gel transition phenomena by forming hydrogels using block copolymers employing the above-mentioned biodegradable polymers or amphiphilic polymers are actively conducted.
U.S. Pat. No. 4,942,035 discloses the problem that polyethylene glycol and polyethylene oxide-polypropylelen oxide-polyethyleneoxide block copolymer (usually called ‘Pluronic’ are not degraded in vivo using the copolymerization of polyalkylene glycol being hydrophilic polymer, polylactide or polyglycolide being biodegradable polyester polymer, and polycaprolactone.
And, U.S. Pat. No. 5,476,909 discloses a biodegradable triblock (A-B-A) copolymer. Hydrophobic blocks (A) are limited as polylactic acid (PLA), polyglycolic acid (PGA), or derivatives thereof. The hydrophilic block (B) is limited as polyethylene glycol (PEG) or derivatives thereof.
Meanwhile, Korean Patent No. 2006-0574341 discloses a pH-sensitive polymer comprising sulfonamide groups, and a preparation method thereof. This patent relates mainly to either a change in the solubility of linear polymers formed by the random copolymerization of sulfonamide monomers with DMAAm or NiPAAm, or the swelling index of cross-linked polymers thereof.
Additionally, Korean Patent No. 2006-0665672 discloses a pH- and temperature-sensitive block copolymer and hydrogels using the same and ionic complex with hydrogel drugs according to ionization and de-ionization of poly (β-amino ester) and poly (amido amine) depending on pH variations, and continuous drug ejection based on the above-mentioned phenomenon while undergoing copolymerization of temperature-sensitive and hydrophilic polymer polyalkylene-based compound, aliphatic polyester polymer being biodegradable polymer and hydrophobic polymer, and poly (β-amino ester) and poly (amido amine) being pH-sensitive polymer through a conventional reaction mechanism such as Michael reaction mechanism. In these multi-block copolymers, it is necessary to examine interaction and safety stability of block copolymer degraded in vivo and drugs.
The above-described prior arts were so designed that a sol-gel transition phenomenon is shown by the use of the block copolymer of the hydrophobic biodegradable polymer with the hydrophilic polymer. The block copolymer when injected in vivo in an aqueous solution form, a sol-state, is changed into a gel state. Thus, the block copolymer was used as a sustained drug delivery system which carries and slowly releases drugs in vivo. However, block copolymer that exhibits a temperature-sensitive sol-gel transition phenomenon cause problems, such as the clogging phenomenon of injection needles occurring during injection before in vivo injection, since in vivo temperature and the temperature of the injection needles are adjusted to the same temperature by thermal equilibrium. In addition, hydrophobic moieties comprised of PLA, PGA, PLGA, PCGA, PCL, or PCLA that are used as biodegradable polymer are reported to exhibit pH-sensitivity. Block copolymer using poly (β-amino ester) having pH-sensitivity is limitedly used as long-term sustained-drug delivery system. However, they are not suitable for practical use in the drug delivery system.
Moreover, in U.S. Pat. No. 6,476,156, there are two main problems. One is a coupling process of PEG, PLA, PGA, and PLC. The other is unsuitable practical use because pH variations in vivo are not considered.